Efficacy of Azoles Antifungals in Treatment of Pityriasis Versicolor

Introduction: Pityriasis versicolor is superficial fungal infection. Topical drugs are often effective in treatment of limited disease while systemic drugs are more suitable in extensive cases. The systemic triazole drugs, itraconazole and fluconazole have shown promising results at different doses. Aims: To assess the efficacy and safety of oral fluconazole combined with ketoconazole shampoo and oral itraconazole in the treatment of Pityriasis versicolor. Methods: The study was conducted at department of Dermatology at Nepalgunj Medical College from March 2019 to February 2020. Total 100 patients of both genders with Pityriasis versicolor were randomly allocated into two groups with 50 patients in each group. Patients in Group I received oral fluconazole 300mg a week for two consecutive weeks along with ketoconazole 2% shampoo twice weekly for two weeks while those in Group II received itraconazole 200mg daily for one week. Efficacy was assessed in terms of negative fungal hyphae. The drug is considered safe if no patients were withdrawn for clinical adverse effects or laboratory abnormalities. Results: In this study age ranged from 18 to 50 years with mean age of 31.1 years in Group I and 31.92 years in Group II. Efficacy was seen in 78% of Group I patients as compared to 54% in Group II patients at two weeks and 94% in Group I and 90% in Group II at four weeks. No significant adverse effects were reported in any of the group. Conclusion: Fluconazole along with ketoconazole shampoo is more effective than itraconazole in treatment of pityriasis versicolor with minimal side effects, at lesser cost.

A comparative study of oral Ketoconazole versus Itraconazole in the treatment of Tinea versicolor

Tinea (pityriasis) versicolor is a superficial fungal infection and one of the most commonly found pigmentary disorders of the skin caused by the yeast Malassezia. Multiple topical as well as systemic therapies are available for treatment. Systemic therapies are used for extensive disease, frequent relapse or where topical agents have failed. The aim that translates the rationale of the study was to compare the efficacy, safety, tolerability and cost effectiveness of oral ketoconazole dose 200mg daily for 7 days versus a single dose of 400 mg of itraconazole in the treatment of tinea versicolor. A total of 64 patients (aged 18-50 years) were selected for the study from the period of June 2019 to November 2019 in the Department of Dermatology and Venereology, Bangabandhu Sheikh Mujib Medical University, Bangladesh. Cases having extensive involvement were diagnosed clinically and confirmed by wood's lamp and KOH microscopy was taken. Patients were randomly allocated into equal groups. Group A was given oral ketoconazole dose 200mg daily for 7 days and Group B has given a single dose of 400 mg of itraconazole. 47 (73.4%) male and 17(26.6%) female were included in the study. The mean age of group A was 29.2(SD±8.6) and in group B 28.2(SD±8.5) years. The mean duration of the disease in group A was 3.9(±2.7) months and 3.5(±2.2) months in group B. In group A clinical responders was found cure 25(78.1%), improvement 5(15.6%) and failure in 2(6.2%) and in group B it was found cure 22(68.8%), improvement 7(21.87%) and failure 3(9.4%) at one month. At two months in the group A clinical responder was found to cure 22(68.8%), improvement 5(15.6%), failure in 3(9.4%) and relapse 2(6.2%). In group B it was found cure 18(56.2%), improvement 6(18.75%), failure 4(12.5%) and relapse 4(12.5%). Both oral ketoconazole dose 200mg daily for 7 days versus single dose 400 mg of itraconazole can be effective in the treatment of tinea versicolor with extensive involvement. CBMJ 2020 July: Vol. 09 No. 02 P: 26-33

Depth of Response to ≥VGPR at Completion of Induction Influences Outcome Post ASCT, on Behalf of the Tunisian Myeloma Study Group

Background: High dose Melphalan (HDM) and autologous stem cell transplantation (ASCT) is a standard care for Myeloma ≤ 65 years. Studies have demonstrated that depth of response prior to ASCT does not impact outcome post ASCT, e.g. solely depth of response post ASCT matters. However, with improving induction regimens, the questions remains whether patients achieving a deeper response at completion of induction would not perform better post ASCT. ASCT can only be performed in Tunisia if newly diagnosed Multiple Myeloma (NDMM) achieves at least PR; we therefore sought to report the national Tunisian experience. Patients and Methods: NDMM aged ≤65 years received three cycles of Thalidomide (200mg daily) and Dexamethasone, followed by HDM and ASCT.52% received maintenance therapy for 12 months with Thalidomide, from 3 months post transplantation. Non responders to TD induction were salvaged with Lenalidomide or Bortezomib-based regimen. The response was assessed based on IMWG response criteria. The study is performed in ITT. Results: 202 consecutive pts were included between April 2012 and December 2014. The median age was 56 yrs (range, 25-65), sex ratio was 1.R-ISS stage was 3 in 27.5%. 21% had high risk cytogenetic (by Conventional karyotyping and FISH). Renal failure was observed in 17%. ORR after induction was 71% with 12% CR, 17% VGPR. 22% failed to obtain PR following TD induction, and 51% of whom received salvage induction therapy (ST) with 72% that further reached ≥PR after ST. Overall, 141 pts (70%) underwent ASCT, 121 of whom had evidence of chemo-sensitive MM at completion of induction. 16% were transplanted in CR, 22% in VGPR and 62% in PR. At 3 months post-ASCT, the ORR in induction chemo-sensitive MM was 89%: 36% CR, 20% VGPR, and 33% PR. With a median follow-up post-ASCT of 27 months, the OS, PFS and EFS at 27 months were 82%, 60.5% and 56%, respectively. Maintenance treatment was significantly associated with longer PFS only in MM who did not achieve CR (29 versus 9 months, p=0.004). MM with improved response post-ASCT had a significantly longer PFS (39 versus 21 months, p=0.003) and EFS (39 versus 20 months, p=0.002). Importantly, achieving CR before (p=0.03) and after ASCT (p<0.0001) was also predictive for prolonged EFS. Early relapses/progressions (less than 18 months) was the sole predictive factor of adverse OS in our study (p=0.01). In multivariate analysis, ISS stage 3 was the sole independent predictor of induction failure (p=0.003). Importantly, predictive factors of achievement of CR post-ASCT comprised absence of delay farther to 4 months from completion of induction (p=0.006; OR = 4.54) and achievement of at least VGPR status before transplant (p=0,001; OR = 4.09). Conclusion: Achievement of at least VGPR at completion of induction improved response after ASCT and consequently influenced the post-ASCT outcome. Therefore, depth of response matters before and after ASCT, and validates in some extent the concept of induction salvage therapy prior to ASCT for patient not reaching response. Disclosures Leleu: TEVA: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; LeoPharma: Honoraria; Pierre Fabre: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

Cutaneous histoplasmosis disclosing an HIV-infection

Histoplasmosis is a systemic mycosis endemic in extensive areas of the Americas. The authors report on an urban adult male patient with uncommon oral-cutaneous lesions proven to be histoplasmosis. Additional investigation revealed unnoticed HIV infection with CD4+ cell count of 7/mm3. The treatment was performed with amphotericin B, a 2065 mg total dose followed by itraconazole 200mg/daily plus antiretroviral therapy with apparent cure. Histoplasmosis is an AIDS-defining opportunistic disease process; therefore, its clinical diagnosis must drive full laboratory investigation looking for unnoted HIV-infection.

Overcoming tumor antigen anergy in human malignancies using the novel indeolamine 2,3-dioxygenase (IDO) enzyme inhibitor, 1-methyl-D-tryptophan (1MT)

3004 Background: The limited effect of cancer immunotherapy is due to the tumor's ability to induce host anergy towards its antigens. The enzyme indoleamine 2,3-dioxygenase (IDO) is thought to play a key role in anergy induction. IDO metabolizes tryptophan (trp) into immunosuppressive metabolites such as kynurenine (kyn). The oral IDO inhibitor, 1-methyl-D-tryptophan (1MT), was studied in preclinical models. The preclinical data support the activity of 1-MT in preventing T-cell anergy in TDLN, slowing growth of LLC mouse xenografts, and synergizing with chemotherapy in regression of autochthonous breast tumors in MMTV-Neu mice. This led to a phase I first-in-man trial using 1-MT in solid tumors. Methods: This is a phase I study treating adults with refractory solid malignancies. Patients are treated with up to 6 consecutive 28-day cycles starting at 200mg once daily. A 3+3 dose escalation to MTD is used. PK analysis, weekly labs, and CT scans every 2 cycles were done. Correlative studies include serum kyn/trp levels, T-reg cell quantification by flow, tumor IDO expression by IHC, and humoral immune response using a proprietary tumor antigen microarray. Results: Ten pts have recieved 1-MT at 200mg daily. Tumors treated included 1 esophageal, 1 peritoneal, 3 melanomas, 2 sarcomas, and 3 NSCLC. PK results show good bioavailability and a t1/2 of 2–4 hrs. Of the 7 evaluable pts, 4 had SD and 3 had PD. Attributable toxicities were 1 case of grade 1 fatigue and 2 cases of grade 2 hypophysitis. Both cases occurred in pts who received prior immunotherapies. Six new pts without prior immunotherapy were enrolled at the 200mg dose level. Five pts remain on treatment currently. Three pts had decreased T-reg cells after treatment with 1MT and 4 pts showed marked CRP increases. One pt had increased autoantibody titers against 3 tumor antigens compared to baseline. Conclusions: 1-MT appears to be an active, orally bioavailable, and reasonably well tolerated immunomodulator at 200mg daily. Development of hypophysitis in 2 patients indicates the drug can break tolerance resulting in autoimmunity. Enrollment to the trial continues. Future trials will combine 1-MT with other immunotherapies and chemotherapies for solid tumors. [Table: see text]

Amiodarone – induced pulmonary nodules mimiking metastatic lung disease – investigation by somatostatin radio peptide scaning

A 61 year old former paramedic presented to A&E complaining of palpitations. He was found to be in atrial fibrillation, which reverted spontaneously to sinus rhythm. A chest x-ray taken at that time showed multiple pulmonary nodules consistent with metastatic malignancy (Figure 1). In the past he had been treated with amiodarone 200mg daily for 6 years following a previous diagnosis of atrial fibrillation, which had been attributed to alcoholic cardiomyopathy. He had discontinued the drug 8 months earlier, after selfdiagnosing hypotension and bradycardia. A previous chest X-ray, taken before starting amiodarone, was normal.

Treatment of Endometriosis with Reduced Dosage Schedules of Danazol

Experience of the treatment of endometriosis with danazol compares very favourably with the previous use of an oestrogen-progestogen combination in this condition. Symptoms were relieved more rapidly and for longer periods of time. The response to various dose regimes of danazol reveals that 200mg daily may be adequate for most cases.